Severe respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants <2 years-old. Here we describe that high-fiber diet protects mice from RSV infection. This effect was dependent on intestinal microbiota and production of acetate. Oral administration of acetate mediated interferon-β (IFN-β) response by increasing expression of interferon-stimulated genes in the lung. These effects were associated with reduction of viral load and pulmonary inflammation in RSV-infected mice. Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice. Activation of Gpr43 in pulmonary epithelial cells reduced virus-induced cytotoxicity and promoted antiviral effects through IFN-β response. The effect of acetate on RSV infection was abolished in Gpr43 − / − mice. Our findings reveal antiviral effects of acetate involving IFN-β in lung epithelial cells and engagement of GPR43 and IFNAR.

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Breast cancer is one of the leading types of cancer worldwide, and the search for new treatment options are crucial. Nonsteroidal anti-inflammatory drugs (NSAIDs) -specially ibuprofen and diclofenac-, have shown antitumoral effect against several types of cancer. The synthesis of organometallic compounds has shown significant improvements in pharmacological properties and efficacy of organic molecules. Two zinc II ternary complexes containing the NSAIDs diclofenac and ibuprofen and nicotinamide neutral linker (Nic) were obtained by the two-step solvent metalligand complexation method. The compounds Zn2(Diclof)4(Nic)2 (complex 1) and Zn2(Ibup)4(Nic)2 (complex 2) were tested in breast cancer cell lines (4T1, MCF-7 and MDA-MB-231) to evaluate their cytotoxicity, comparing to ibuprofen and diclofenac as controls. We found that both complex 1 and 2 exerted more than 60% reduction in 4T1 viability at 250µM, and complex HIGHLIGHTS• Diclofenac and ibuprofen-derived complexes decrease viability of breast cancer cell lines• Complex 1 presented antitumor effect in all breast cancer cell lines tested including on triple negative cell line (MDA-MB-231) (IC50 202µM)• Complex 1 was selective for both 4T1 and MDA-MB-231 cells Da Silva, E.F.; et al.